The age-determined decay in the ablity to mount a T-cell-mediated antibacterial immune response will be studied employing murine listeriosis as a model. The results obtained thus far suggests that in the case of a long-lived mouse strain, a period of maturation of resistance to listeriosis from birth to about 8 months of age is followed by a slow and progressive decline in resistance up to 20 months of age. Sampling from this population of mice in a longitudinal study initiated this year will be continued until senescence. The results obtained will be utilized in selecting age groups for a cross-sectional analysis to determine the cellular basis of the age-determined decline in antibacterial resistance. The possibility of a malfunction at the levels of the T-cell response will be investigated by adoptive transfer studies that will employ limiting dilution analysis and cell mixture experiments. These studies will be complemented by in vitro culturing of lymphocytes in the prescence of specific antigen, or nonspecific polyclonial mitogens, with the view to detecting an age-determined decline in mitogenic responsiveness. The possibility of an age-determined defect at the level of macrophage function will be studied by culturing macrophages from young and aged mice in vitro, and measuring the rate and extent of the acquisition of microbicidal activity by these cells under the influence of lymphokines.